Primary Objectives:~• To assess the intracranial objective response rate (iORR), defined as intracranial CR + PR per modified RECIST 1.1 criteria, of nivolumab + relatlimab (nivo+rela) in subjects with MBM and treatment naïve to anti-PD-1 agents in the metastatic setting.~Secondary Objectives:~To determine the safety of the combination of nivo+rela~To assess the clinical benefit rate (CBR), defined as CR + PR + SD >6 months, of the combination~To determine overall response rates (intracranial + extracranial), DoR, PFS, and using a modified version of iRANO and compared to modified RECIST v1.1 and Response Assessment in Neuro-oncology - Brain Metastases (RANO-BM) for patients treated with nivo+rela~To determine the 1-year intracranial progression-free survival rate for the combination of nivo+rela~To determine overall survival~Advanced MRI imaging to assess for edema, tumor response, and predictors of response and radiation necrosis~To evaluate the brain-specific safety and tolerability of the combination regimen in subjects with or without SRT received prior to study entry, or on study~To evaluate changes in neurocognitive function and health-related quality of life~To assess available tumor tissue - intracranial and/or extra cranial - in specimens obtained at baseline (archival and/or fresh tissue), on treatment, and at time of progression~To assess immune cell subsets by flow cytometry, TCR NGS for diversity and clonality, cytokine expression, cfDNA from peripheral blood.~Exploratory Endpoints:~Radiotherapy-assisted PFS defined as time from study treatment initiation to the first occurrence of disease progression or death from any cause, whichever occurs first, as determined by the investigator according to RECIST v1.1 modified by excluding ≤ 5 lesions that can be treated by SRT from the sum of largest diameters from baseline onwards.~To explore the association between baseline and on-treatment gut microbiome features with response and toxicity~To understand the association between habitual diet and gut microbiome features in this study population.~To explore predictors of biological response through the change in metabolic parameters
To learn if giving nivolumab in combination with relatlimab can help to control melanoma that has spread to the brain (melanoma with brain metastases). The safety and side effects of the study drug combination will also be studied.