This timing for these molecular events is consistent with the very high concordance that has been observed for activating mutations in the RAS-RAF-MEK-ERK signaling pathway between MBMs, extracranial metastases, and primary tumors.15,16 Indeed, this result is also consistent with the clinical activity that has been observed with FDA-approved BRAF inhibitors in metastatic melanoma patients with a BRAFV600 mutation and brain metastases, as will be described below. Here, BRAF is linked to metastatic melanoma.