REMASTer: REcurrent Brain Metastases After SRS Trial

Inclusion Criteria:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Patients with radiographically proven (by gadolinium-enhanced [Gd-] MRI) parenchymalbrain metastases from histologically confirmed non-central nervous system (CNS)cancer.

2. Patients with a "targetable", bidimensionally-measurable, intracranial lesion thatis radiographically recurrent after previous treatment with SRS +/- surgery (craniotomy or LITT). To classify a lesion as radiographically progressive, thelesion must demonstrate a ≥ 25% increase in size following treatment based on theNeuro-Oncology Criteria of Tumor Response for CNS Tumors. To be "targetable" forthis study, the lesion should be coverable through a planned single LITT trajectoryand thus have a maximum perpendicular diameter (perpendicular to the lasertrajectory) of 3 cm. An intra-operative decision to utilize two trajectories isacceptable and patient may remain on study.

3. Patient must be at least 3 months post initial SRS treatment of the target lesion

4. Target lesion must be amenable to undergo surgical biopsy and LITT treatment asdetermined by the treating neurosurgeon.

5. Frozen pathology diagnosis must be attainable.

6. Patient must be symptomatically stable for a minimum of 3 days prior to theprocedure date on a on a max total daily steroid dose equivalent to 4mg ofDexamethasone.

7. ≥18 years of age

8. KPS ≥70

9. Patient is able and willing to complete study requirements

10. Patients with adequate hematologic parameters (all tests to be performed within <4weeks of biopsy):

11. ANC ≥ 1.5 X 109/L

12. Platelet count ≥ 100 x 109/L

13. Blood chemistry laboratory value for serum creatinine < 1.5 x ULN (test to beperformed within <4 weeks of biopsy)

14. Female patients must have a negative serum pregnancy test at screening. (Notapplicable to patients with bilateral oophorectomy and/or hysterectomy or to thosepatients who are postmenopausal)

15. All patients of reproductive potential must agree to use an effective method ofcontraception during the study

16. Patients must be accessible for follow-up

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Patients with greater than 3 progressing lesions at time of enrollment. To classifyas a radiographically progressive, lesion must demonstrate a ≥ 25% increase in sizefollowing treatment based on the RANO criteria. Of note, there is no exclusion fortotal number of metastases. However, only one lesion can be selected to be thetargeted lesion and this lesion alone may be ablated during the study procedure.

2. Patients with concomitant newly diagnosed intracranial metastases (concurrent withthe targetable radiographically progressive lesion), as these will requireprioritized and different treatment approaches.

3. Prior bevacizumab use within 4 weeks of study initiation

4. Patients with additional concurrent malignancies requiring active treatment, exceptnon-melanoma skin cancer, or in-situ cancer of the cervix

5. Patients with a serious active infection or other serious underlying medicalconditions that would impair the ability of the patient to complete the protocolrelated QOL questionnaires and cognition assessments

6. Inability to tolerate or contraindication to steroid therapy (i.e., dexamethasone)

7. Deemed ineligible or unable to tolerate SRS therapy by treating neurosurgeon and/orradiation oncologist

8. Patients with any condition that would prohibit them from undergoing a surgicalprocedure, at the discretion of the treating physician team

9. Patients unwilling or unable to give consent for participation

10. Patients unable to comply with study requirements

11. Patients with diffuse leptomeningeal disease

12. Patients with rapidly progressing extracranial disease