Stereotactic Brain-directed Radiation With or Without Aguix Gadolinium-Based Nanoparticles in Brain Metastases

Inclusion Criteria:

• Participants must have a biopsy proven solid malignancy and at least oneintracranial measurable lesion spanning ≥5mm in maximal unidimensional size andradiographically consistent with or pathologically proven to be a brain metastasisAND meet one of the following additional criteria regarding the primary site ornature of the intracranial disease:

• Melanoma with intracranial growth consistent with tumor progression despiteimmunotherapy

• Gastrointestinal primary

• HER2 positive breast cancer (subtype assessed using most representative tissueavailable in opinion of enrolling clinician and/or study PI)

• Cystic metastases

• Metastases ≥2cm in maximal unidimensional size

• Locally recurrent metastases after prior stereotactic radiation

• Locally recurrent metastases after prior whole brain radiation *Patients withmetastases from melanoma, GI primaries, or HER2+ breast cancer, as well asthose with cystic metastases or metastases ≥2cm in maximal unidimensional size,who have local recurrences after prior brain-directed radiation can only betreated in the strata permitting prior radiation (last two strata above)

• Age ≥18 years at diagnosis of brain metastases

• Estimated glomerular filtration rate of ≥ 60 mL/min/1.73m2

• Karnofsky performance status of at least 70 (i.e. at minimum, "cares for self" but "unable to carry on normal activity or do active work")

• Estimated survival based on extracranial disease of at least 3 months in the opinionof the enrolling clinician and/or study PI

• Ability to understand and the willingness to sign a written informed consentdocument

• The effects of AGuIX on the developing human fetus are unknown. For this reason,women of child-bearing potential must agree to use adequate contraception prior tostudy entry and for the duration of the therapeutic component of study participation

Exclusion Criteria:

• Participants who cannot undergo a brain MRI

• Participants who cannot receive gadolinium

• Participants with widespread, definitive leptomeningeal disease

• Patients requiring radiation to either >10 targets (if naïve to whole brainradiation) or >20 targets (if whole brain radiation has been given previously) perthe discretion of the treating clinician and/or study PI

• Pregnant women are excluded from this study because of the potential deleteriouseffects of gadolinium on the developing fetus. Because there is an unknown butpotential risk for adverse events in nursing infants, women who are breastfeedingare not eligible for this study

• In cohorts who have received prior brain-directed radiation, patients are noteligible for this study if they have active (at the time of protocol screening)brain metastases that require radiation that are in or within 1.0cm of thebrainstem, eyes, optic nerves, or optic chiasm if the juxtaposed organ at risk (i.e.brainstem, eyes, optic nerves, or optic chiasm) has previously received either >6.0Gy in a single fraction or, if prior radiation was fractionated, a cumulative dosein 2.0 Gy equivalents, using an alpha/beta ratio of 2, of >40.0 Gy. In addition, allpatients who have had prior brain-directed radiation, regardless oftechnique/dose/fractionation, are not eligible for the study until written approvalis provided by the study/site PI