Comparing the Addition of Radiation Either Before or After Surgery for Patients With Brain Metastases

Inclusion Criteria:

• Radiographic confirmation of 1-4 brain metastases, one of which requires resection,as defined by magnetic resonance imaging (MRI) with contrast obtained within 14 daysprior to registration

• The maximum diameter of the lesion to be resected on the post-contrast MRI, asmeasured on any orthogonal plane (axial, sagittal, coronal), must measure >= 2.0 cm and =< 5.0 cm.

• The maximum diameter of any lesions which will not be resected must be =< 4.0cm in maximum diameter

• Known active or history of invasive non-central nervous system (CNS) primary cancerbased on documented pathologic diagnosis within the past 3 years

• All brain metastases must be located >= 5 mm from the optic chiasm and outside thebrainstem

• Patient is able to medically tolerate surgery and SRS

• Lesions chosen for surgical therapy must be deemed appropriate targets for safe,gross total resection by the treating surgeon

• History/physical examination within 14 days prior to registration

• Age >= 18

• Karnofsky performance status (KPS) >= 60 within 14 days prior to registration

• A negative urine or serum pregnancy test (in persons of childbearing potential)within =< 14 days prior to registration. Childbearing potential is defined as anyperson who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal

• Participants who are sexually active must agree to use medically acceptable forms ofcontraception during treatment on this study to prevent pregnancy

• The patient or a legally authorized representative must provide study-specificinformed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information

Exclusion Criteria:

• Prior cranial radiotherapy, including whole brain radiotherapy, or SRS to theresection site

• Note: The index lesion to be resected cannot have been previously treated withSRS (i.e. repeat radiosurgery to the same location/lesion is not allowed onthis protocol). Previous SRS to other lesions is allowed

• Evidence of leptomeningeal disease (LMD)

• Note: For the purposes of exclusion, LMD is a clinical diagnosis, defined aspositive cerebrospinal fluid (CSF) cytology and/or unequivocal radiologic orclinical evidence of leptomeningeal involvement. Patients with leptomeningealsymptoms in the setting of leptomeningeal enhancement by imaging (MRI) would beconsidered to have LMD even in the absence of positive CSF cytology. Incontrast, an asymptomatic or minimally symptomatic patient with mild ornonspecific leptomeningeal enhancement (MRI) would not be considered to haveLMD. In that patient, CSF sampling is not required to formally exclude LMD, butcan be performed at the investigator's discretion based on level of clinicalsuspicion

• Any medical conditions which would make this protocol unreasonably hazardous,including, but not limited to: contraindications to general endotracheal anesthesia;intracranial surgery; and stereotactic radiosurgery

• Primary histology of germ cell tumor, small cell carcinoma or lymphoma

• More than one brain metastasis planned for resection

• Inability to undergo MRI with contrast

• Planned administration of cytotoxic chemotherapy or tyrosine/multi-kinase inhibitorswithin the 3 days prior to, the day of, or within 3 days after the completion of SRS

• Note: chemotherapy and immunotherapy outside of this window are allowed