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Median follow\u2010up (if alive) was over 7\u00a0years (range: 1\u00a0month to 11\u00a0years). The site of initial progression was identifiable in 80% of relapsing patients.<jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>progression was a component of systemic melanoma relapse in 59\/402 patients (15% overall). In 34\/402 patients (9%)<jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>progression represented the initial site of treatment failure.<jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>progression was a component of initial progression in 27% of all patients whose melanoma relapsed (59\/221). The risk of<jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>progression was highest within 3\u00a0years of randomization. The difference in<jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>progression rates between treatment arms was not significant (<jats:styled-content style=\"fixed-case\">BCT<\/jats:styled-content>\u00a0=\u00a025,<jats:styled-content style=\"fixed-case\">HDI<\/jats:styled-content>\u00a0=\u00a034,<jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.24). Lymph node macrometastases strongly associated with<jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>progression (<jats:italic>P\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.001), while ulceration and head and neck primaries were not significant predictors. This retrospective analysis of the S0008 trial identified a high brain metastasis rate (15%) in regionally advanced melanoma patients. 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